Correction: Limited Clinical Utility of Remote Ischemic Conditioning in Renal Transplantation: A Meta-Analysis of Randomized Controlled Trials.

[This corrects the article DOI: 10.1371/journal.pone.0170729.].

Identification of hub miRNA biomarkers for bladder cancer by weighted gene coexpression network analysis.

Bladder cancer (BC) is a common urinary system tumor with high aggressiveness, and it results in relatively high mortality due to a lack of precise and suitable biomarkers. In this study, we applied the weighted gene coexpression network analysis method to miRNA expression data from BC patients, and screened for network modules associated with BC progression. Hub miRNAs were selected, followed by functional enrichment analyses of their target genes for the most closely related module. These hub miRNAs were found to be involved in several functional pathways including pathway in cancer, regulation of actin cytoskeleton, PI3K-Akt signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, Wnt signaling pathway, proteoglycans in cancer, focal adhesion and p53 signaling pathway via regulating target genes. Finally, their prognostic significance was tested using analyses of overall survival. A few novel prognostic miRNAs were identified based on expression profiles and related survival data. In conclusion, several miRNAs that were critical in BC initiation and progression have been identified in this study. These miRNAs, which may contribute to a comprehensive understanding of the pathogenesis of BC, could serve as potential biomarkers for BC prognosis or as new therapeutic targets.

A Molecular Signature of Two Long Non-Coding RNAs in Peripheral Blood Predicts Acute Renal Allograft Rejection.

BACKGROUND/AIMS: Acute rejection (AR) is a major complication post renal transplantation, with no widely-accepted non-invasive biomarker. This study aimed to explore the expression profiles of long non-coding RNAs (lncRNAs) in the peripheral blood (PB) of renal transplant recipients and their potential diagnostic values. METHODS: The genome-wide lncRNA expression profiles were analyzed in 150 PB samples from pediatric and adult renal transplant (PRTx and ARTx) cohorts. The diagnostic performance of differentially expressed lncRNA was determined using receiver operator characteristic curve, with area under the curve (AUC) and 95% confidential interval (CI). Finally, a risk score was constructed with logistical regression model. RESULTS: A total of 162 lncRNAs were found differentially expressed in PRTx cohort, while 163 in ARTx cohort. Among these identified lncRNAs, 23 deregulated accordingly in both cohorts, and could distinguish AR recipients from those without AR. Finally, a risk score with two most significant lncRNAs (AF264622 and AB209021) was generated and exhibited excellent diagnostic performance in both PRTx (AUC:0.829, 95% CI:0.735-0.922) and ARTx cohorts (AUC: 0.889, 95% CI: 0.817-0.960). CONCLUSION: A molecular signature of two lncRNAs in PB could serve as a novel non-invasive biomarker for the diagnosis of AR in both pediatric and adult renal transplant recipients.

Remote ischemic conditioning for the prevention of contrast-induced acute kidney injury in patients undergoing intravascular contrast administration: a meta-analysis and trial sequential analysis of 16 randomized controlled trials.

OBJECTIVE: We conducted this meta-analysis to examine the effect of remote ischemic conditioning (RIC) on contrast-induced acute kidney injury (CI-AKI) in patients undergoing intravascular contrast administrationon. METHODS: Pubmed, Embase, and Cochrane Library were comprehensively searched to identify all eligible studies by 15th March, 2017. Risk ratio (RR) and weighted mean difference with the corresponding 95% confidence intervals (CI) were used to examine the treatment effect. The heterogeneity and statistical significance were assessed with Q-test and Z-test, respectively. RESULTS: A total of 16 RCTs including 2175 patients were eventually analyzed. Compared with the control group, RIC could significantly decrease the incidence of CI-AKI (RR=0.58; 95% CI: 0.46, 0.74; P < 0.001), which was further confirmed by the trial sequential analysis. Subgroup analyses showed that remote ischemic preconditioning (RIPrC) and remote ischemic postconditioning (RIPoC) were both obviously effective, and perioperative hydration might enhance the efficiency of RIC. RIC also significantly reduced the major adverse cardiovascular events within six months. CONCLUSION: RIC, whether RIPrC or RIPoC, could effectively exert renoprotective role in intravascular contrast administration and reduce the incidence of relevant adverse events.

A BAP1 Mutation-specific MicroRNA Signature Predicts Clinical Outcomes in Clear Cell Renal Cell Carcinoma Patients with Wild-type BAP1.

Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent histologic subtype of kidney cancers in adults, which could be divided into two distinct subgroups according to the BRCA1 associated protein-1 (BAP1) mutation status. In the current study, we comprehensively analyzed the genome-wide microRNA (miRNA) expression profiles in ccRCC, with the aim to identify the differentially expressed miRNAs between BAP1 mutant and wild-type tumors, and generate a BAP1 mutation-specific miRNA signature for ccRCC patients with wild-type BAP1. Methods: The BAP1 mutation status and miRNA profiles in BAP1 mutant and wild-type tumors were analyzed. Subsequently, the association of the differentially expressed miRNAs with patient survival was examined, and a BAP1 mutation-specific miRNA signature was generated and examined with Kaplan-Meier survival, univariate and multivariate Cox regression analyses. Finally, the bioinformatics methods were adopted for the target prediction of selected miRNAs and functional annotation analyses. Results: A total of 350 treatment-naïve primary ccRCC patients were selected from The Cancer Genome Atlas project, among which 35 (10.0%) subjects carried mutant BAP1 and had a shorter overall survival (OS) time. Furthermore, 33 miRNAs were found to be differentially expressed between BAP1 mutant and wild-type tumors, among which 11 (miR-149, miR-29b-2, miR-182, miR-183, miR-21, miR-365-2, miR-671, miR-365-1, miR-10b, miR-139, and miR-181a-2) were significantly associated with OS in ccRCC patients with wild-type BAP1. Finally, a BAP1 mutation-specific miRNA signature consisting of 11 miRNAs was generated and validated as an independent prognostic parameter. Conclusions: In summary, our study identified a total of 33 miRNAs differentially expressed between BAP1 mutant and wild-type tumors, and generated a BAP1 mutation-specific miRNA signature including eleven miRNAs, which could serve as a novel prognostic biomarker for ccRCC patients with wild-type BAP1.

Limited Clinical Utility of Remote Ischemic Conditioning in Renal Transplantation: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: We conducted this meta-analysis of randomized controlled trials (RCTs) to investigate whether remote ischemic conditioning (RIC) could improve graft functions in kidney transplantation. METHODS: PubMed, Web of Science, and Cochrane Library were comprehensively searched to identify all eligible studies by October 5, 2016. The treatment effects were examined with risk ratio (RR) and weighted mean difference with the corresponding 95% confidence intervals (CI). The statistical significance and heterogeneity were assessed with both Z-test and Q-test. RESULTS: A total of six RCTs including 651 recipients, were eventually identified. Compared to the controls, RIC could reduce the incidence of delayed graft function (DGF) after kidney transplantation (random-effects model: RR = 0.89; fixed-effect model: RR = 0.84). However, the decrease did not reveal statistical significance. The subgroup analysis by RIC type demonstrated no significant difference among the three interventions in protecting renal allografts against DGF. Furthermore, no significant difference could be observed in the incidence of acute rejection, graft loss, 50% fall in serum creatinine, as well as the estimated glomerular filtration rate and hospital stay between the RIC and Control groups. CONCLUSIONS: This meta-analysis suggested that RIC might exert renoprotective functions in human kidney transplantation, and further well-designed RCTs with large sample size are warranted to assess its clinical efficacy.

Expression Profiles and Clinical Significance of MicroRNAs in Papillary Renal Cell Carcinoma: A STROBE-Compliant Observational Study.

Papillary renal cell carcinoma (pRCC) is the second most prevalent subtype of kidney cancers. In the current study, we analyzed the global microRNA (miRNA) expression profiles in pRCC, with the aim to evaluate the relationship of miRNA expression with the progression and prognosis of pRCC.A total of 163 treatment-naïve primary pRCC patients were identified from the Cancer Genome Atlas dataset and included in this retrospective observational study. The miRNA expression profiles were graded by tumor-node-metastasis information, and compared between histologic subtypes. Furthermore, the training-validation approach was applied to identify miRNAs of prognostic values, with the aid of Kaplan-Meier survival, and univariate and multivariate Cox regression analyses. Finally, the online DAVID (Database for Annotation, Visualization, and Integrated Discover) program was applied for the pathway enrichment analysis with the target genes of prognosis-associated miRNAs, which were predicted by 3 computational algorithms (PicTar, TargetScan, and Miranda).In the progression-related miRNA profiles, 26 miRNAs were selected for pathologic stage, 28 for pathologic T, 16 for lymph node status, 3 for metastasis status, and 32 for histologic types, respectively. In the training stage, the expression levels of 12 miRNAs (mir-134, mir-379, mir-127, mir-452, mir-199a, mir-200c, mir-141, mir-3074, mir-1468, mir-181c, mir-1180, and mir-34a) were significantly associated with patient survival, whereas mir-200c, mir-127, mir-34a, and mir-181c were identified by multivariate Cox regression analyses as potential independent prognostic factors in pRCC. Subsequently, mir-200c, mir-127, and mir-34a were confirmed to be significantly correlated with patient survival in the validation stage. Finally, target gene prediction analysis identified a total of 113 target genes for mir-200c, 37 for mir-127, and 180 for mir-34a, which further generated 15 molecular pathways.Our results identified the specific miRNAs associated with the progression and aggressiveness of pRCC, and 3 miRNAs (mir-200c, mir-127, and mir-34a) as promising prognostic factors of pRCC.

Effect of high-dose erythropoietin on graft function after kidney transplantation: a meta-analysis of randomized controlled trials.

PURPOSE: Current evidence suggests that preconditioning with erythropoietin (EPO) can protect against ischemia reperfusion injury in rodents. However, randomized controlled trials (RCTs) assessing the efficacy and safety of high-dose EPO in kidney transplantation have yielded inconclusive results. Herein, we performed a meta-analysis of RCTs to assess whether the administration of high-dose EPO can improve graft function and the potential adverse events. METHODS: Relevant RCT studies that investigated high-dose EPO on graft function after kidney transplantation were comprehensively searched in Pubmed, Embase, and Cochrane Library until July 10, 2014. All statistical analyses were performed using Review Manager 5.0 and STATA 12.0. RESULTS: A total of 4 RCTs involving 356 patients were identified. Comprehensively, a trend of reduction in the incidence of delayed graft function could be observed in the EPO group (EPO vs. placebo groups: RR=0.88); however, the result did not reach the significance level (95% CI, 0.72-1.08; P=0.21). Furthermore, no significant difference in the incidences of adverse events was observed between the two groups. CONCLUSIONS: The current meta-analysis indicates that the administration of high-dose EPO is, to some extent, prone to protect kidney function without increasing the susceptibility to adverse events.